title: Critical role of the nucleolus in activation of the p53-dependent postmitotic checkpoint.
abstract: Cells eventually exit from mitosis during sustained arrest at the spindle checkpoint, without sister chromatid separation and cytokinesis. The resulting tetraploid cells are arrested in the subsequent G1 phase in a p53-dependent manner by the regulatory function of the postmitotic G1 checkpoint. Here we report how the nucleolus plays a critical role in activation of the postmitotic G1 checkpoint. During mitosis, the nucleolus is disrupted and many nucleolar proteins are translocated from the nucleolus into the cytoplasm. Among the nucleolar factors, Myb-binding protein 1a (MYBBP1A) induces the acetylation and accumulation of p53 by enhancing the interaction between p300 and p53 during prolonged mitosis. MYBBP1A-dependent p53 activation is essential for the postmitotic G1 checkpoint. Thus, our results demonstrate a novel nucleolar function that monitors the prolongation of mitosis and converts its signal into activation of the checkpoint machinery.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: Naohiro
authors.initials: N
authors.lastname: Katagiri
authors.forename: Takao
authors.initials: T
authors.lastname: Kuroda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishimoto
authors.forename: Kazuho
authors.initials: K
authors.lastname: Nishimura
authors.forename: Takuya
authors.initials: T
authors.lastname: Kumazawa
authors.forename: Naoya
authors.initials: N
authors.lastname: Iwasaki
authors.forename: Keiji
authors.initials: K
authors.lastname: Kimura
authors.forename: Junn
authors.initials: J
authors.lastname: Yanagisawa
mesh_terms: D000107:Acetylation; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000378:metabolism*; D004268:DNA-Binding Proteins; D016193:G1 Phase; D055785:Gene Knockdown Techniques; D006801:Humans; D008938:Mitosis; D015739:Nocodazole / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism*; D011123:Polyploidy; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C491719:MYBBP1A protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors; D015739:Nocodazole